Several studies have suggested that genetics plays an unusually strong role in autoimmune disorders and an even stronger role in both fibromyalgia and chronic fatigue syndrome. At the recent IACFS/ME conference in Ottawa Dr. Clauw stated that aside from single gene mutation disorders that genetics may play a stronger role in FM than any other disorder. A recent paper by the Lights suggested that ME/CFS may have a similarly strong genetic component. This is intriguing given the theory that autoimmune disorders in women may be largely driven by genetic alterations in their X chromosomes. Could a similar process be occurring in FM and CFS?

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I hadnt thought of that before, but it makes perfect sense. Why do women get ME/CFS at a rate of 2 to 1 compared to men? Because they have double the chance, with both their sex hormones being X compared to men with one X and one Y. Its ironic, because from what ive read of the male Y chromosome its the most degenerated, corrupt chromosome of the lot. But the problem might lie in the X chromosome.

The X Chromosome theory is a major theory for autoimmunity in women. It is a VERY complicated theory but it has caught on big time. The high genetic susceptibility in CFS and FM and autoimmunity makes me wonder if a similar genetic problem exists in all three.

I saw an episode of Mystery Diagnosis where a woman had CFS symptoms, had been brushed off by several doctors, and was not getting better under care of F&F Center. She would remit during pregnancy and relapse afterward. She finally found a doctor who solved the problem. I think it was estrogen supplements, but I'm not 100% positive. Her blood tests did not show her as below normal. But the doctor theorized that because her estrogen increased during pregnancy, maybe this would also fix the problem.

Why women are far more likely to get autoimmune disorders suggests to me this hypothesis: Women are designed with an extra "program" or capacity, to develp a human embryo into a baby. This other life is a different life form with whom she has blood to blood contact, the closest contact two individuals can have, on a continual basis. Her immune system has to be able to deal with this, to protect both her and a separate individual's system. Then her biological system also must be prepared for nursing and raising multiple children. This is hugely demanding on the female of the species! Whatever diffferences there are to help with these tasks, would apply to women as a whole, whether or not they have children. This is what I am considering as a background for scientific hypotheses, rather than, say, the influence of a particular sex hormone on the immune system. And since men and women are not absolutely different in their systems, these differences don't create completely separate vulnerabilities.

Thanks Cort for another thought provoking article and as more and more research findings come in (and together). Am I right in saying that most Autoimmune diseases are thought to have viral(s) origins in current thought to date. Can't find anything where it is not suggested for all of them.

I saw an episode of Mystery Diagnosis where a woman had CFS symptoms, had been brushed off by several doctors, and was not getting better under care of F&F Center. She would remit during pregnancy and relapse afterward. She finally found a doctor who solved the problem. I think it was estrogen supplements, but I'm not 100% positive. Her blood tests did not show her as below normal. But the doctor theorized that because her estrogen increased during pregnancy, maybe this would also fix the problem.

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Estrogen is a really interesting aspect of all this. CDC researcher Boneva's study suggests big problems with sex hormones are present and other studies have as well. When I asked her about studying hormone levels she said it was very difficult because of the number of people on the pill, changes during pregnancy, etc. and how variable hormone levels are; essentially you have to take several different measurements at the same time of day - which makes it difficult to get people to cooperate.

The fact that she showed 'normal' levels but responded well to it shows that we are in yet another 'grey' area, unfortunately. An online survey of how well women responded to estrogen supplementation would be interesting.

Why women are far more likely to get autoimmune disorders suggests to me this hypothesis: Women are designed with an extra "program" or capacity, to develp a human embryo into a baby. This other life is a different life form with whom she has blood to blood contact, the closest contact two individuals can have, on a continual basis. Her immune system has to be able to deal with this, to protect both her and a separate individual's system. Then her biological system also must be prepared for nursing and raising multiple children. This is hugely demanding on the female of the species! Whatever diffferences there are to help with these tasks, would apply to women as a whole, whether or not they have children. This is what I am considering as a background for scientific hypotheses, rather than, say, the influence of a particular sex hormone on the immune system. And since men and women are not absolutely different in their systems, these differences don't create completely separate vulnerabilities.

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It makes sense Sing! Women have, by their nature, to have more complex and actually stronger immune systems. Women also have higher rates of CFS, FM, autoimmune disorders and some mood disorders. As a laymen it seems pretty clear to me that the chances of immune involvement in each of these types of disorders must be pretty high; in some of them they've uncovered that and in some of them they haven't.

As you note sex hormones interact strongly with the immune system - so you have that layer as well. We know that some men with CFS also respond to testosterone. Its a fascinating area.

I have a related question, Cort, or anyone else here: Do people with autoimmune disorders, either of the innate or the secondary level, as you wrote about, have more trouble with transplants than others do? Do women have more trouble with transplants than men?--There is another question.

Thanks Cort for another thought provoking article and as more and more research findings come in (and together). Am I right in saying that most Autoimmune diseases are thought to have viral(s) origins in current thought to date. Can't find anything where it is not suggested for all of them.

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Thanks Enid. Without being really up on the pathogen/autoimmune link I would guess that pathogens are considered possible factors in many of them and infection appears to be a pretty common trigger. It could be that the immune response cascades out of control after it gets triggered by the pathogen and that the pathogen doesn't matter or it may be that EBV or another virus gets reactivated. I have to say that my memory is that they've been looking at EBV in multiple sclerosis for years and just can't seem to come to a conclusion.

That's an interesting thought too Cort - the immune system cascading out of control. I recall in my lead up thinking why is it not responding and clearing months of a sore throat (also thought how much longer is the hard pressed immune going to cope with this - it didn't of course and produced full blown ME)

I just got this kind of evocative way of summing up 'sickness behavior' ie the body's response to pathogens which results in flu-like symptoms, in a comment from the blog post.

Cort: I came across this interesting article re: sickness behavior which left a lasting impression of the way i think about CFS Quote from the article For the first time it became clear, says Dantzer. Sickness behaviour is like fearit is a state that makes the animal reorganise its priorities. Just as the sight of a predator makes animals release hormones that drive the flight-or-fight response, infection triggers the release of cytokines, which make the animal rest and conserve its resources to fight the infection. And of course, sickness behaviour is not exclusive to ratsthink of the last time you got flu.http://www.biopsychiatry.com/immunesystem/index.html

Why women are far more likely to get autoimmune disorders suggests to me this hypothesis: Women are designed with an extra "program" or capacity, to develp a human embryo into a baby. This other life is a different life form with whom she has blood to blood contact, the closest contact two individuals can have, on a continual basis. Her immune system has to be able to deal with this, to protect both her and a separate individual's system. Then her biological system also must be prepared for nursing and raising multiple children. This is hugely demanding on the female of the species! Whatever diffferences there are to help with these tasks, would apply to women as a whole, whether or not they have children. This is what I am considering as a background for scientific hypotheses, rather than, say, the influence of a particular sex hormone on the immune system. And since men and women are not absolutely different in their systems, these differences don't create completely separate vulnerabilities.

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But wouldn't having this "other" not-self tissue, the fetus, make it advantageous to have a LOWER autoimmune response? It would not be good to have her immune system attack the baby's cells. And even if it set up an autoimmune response in the mother after the baby's birth, that would lower her chances of successfully bearing more children, an evolutionary disadvantage.

I may be wrong, but it is my understanding that if an immune system is attacking the bodies own tissue, there would be Anti Nuclear Antibodies. Because there is usually not large amounts of ANA's in ME, wouldn't it mean the immune system is reacting to something else? For example, a virus, a bacteria or possibly a hormone or other chemical found in the body (not tissue)? Without ANA's this would mean it is different then the majority of autoimmune diseases and it would have to be reacting to something else, possibly something that shouldn't be there.

Cort, your ability to locate and pull together information from diverse sources and synthesize it for us is amazing. Thanks.

It begs the question, if ME/CFS is an autoimmune disorder, what cells are being attacked?

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Thanks Ixchelkali

That is the big question isn't it? We know there are about 80 recognized autoimmune disorders - each of which attacks a DIFFERENT part of the body. That suggests to me that there are at least 80 different auto-antibodies to search for (that we know of) plus there are certainly ones that we don't know of. Which brings up the question - who do you identify auto-antibodies? and how do you search for an auto-antibody to a nervous system protein. It sounds like there are many, many different possibilities here. I wonder a) how you determine which tissues to target and then how do you go about finding auto-antibodies to them?

But wouldn't having this "other" not-self tissue, the fetus, make it advantageous to have a LOWER autoimmune response? It would not be good to have her immune system attack the baby's cells. And even if it set up an autoimmune response in the mother after the baby's birth, that would lower her chances of successfully bearing more children, an evolutionary disadvantage.

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Logically you would think to avoid this auto-immune reaction women's immune systems would be set 'low' - unless that is its more important for it to be set high - in order to avoid infections. Lots of time evolutionary adaptations are maladaptive in one way but more adaptive in another more important way....so women are better at keeping pathogens from babies but are more likely to succumb to auto-immune disorders (probably later in life, I would suppose)......Just an idea

Cort your post 12 - not sickness "behaviour" - one is sick and the immune system (dysfunctional) rendered unable to function correctly spins out of control. The cause to my mind one or many pathogens altering the normal state of response switching the immune system to the autoimmune - just doesn't happen in nature where a host mounts an attack on itself without some extraneous trigger (maybe a genetic weakness/dormant virals passed on but essentially the immune system tipped out of kilter.)